There is an increasing population of humans suffering from different kinds of inflammatory joint diseases. Diseases, which sometimes are impossible to cure, where the treatment is lifelong and where the symptoms often become worse during the years. So far the focus of the treatment has been on trying to find compounds, which reduce the symptoms but not cure the disease or make the disease decline.
One example of such a disease is rheumatoid arthritis (RA), which is characterized by chronic inflammation of the articular synovial tissues initiated by leukocyte infiltration (mainly neutrophils, macrophages and T cells) and secretion of inflammatory cytokines (TNF-alpha, IFN-gamma, IL-I, IL-6), chemokines and destructive enzymes such as matrix metalloproteases. Activation of T cells is believed to be an important pathogenic factor in the disease although its exact role and potential as a therapeutic target has not yet been identified. The abnormal activation of T cells do, however, most likely occur years before the clinical diagnosis of the disease as T cell dependent IgG antibodies specific for immunoglobulin Fc (i.e rheumatoid factors) and citrullinated protein epitopes are highly predictive for disease (1, 2). Importantly, the risk for developing arthritis is dramatically increased in individuals who have both such antibodies and express certain MHC class II molecules, that share a specific peptide pocket, the so called MHC shared epitope (3, 4). The MHC class II region is also the strongest known genetic factor associated with RA. Taken together, these findings argue for a pathogenic role of MHC class II restricted autoreactive T cells. It has however been difficult to identify a single specificity of such T cells although T cell reactivity to several autoantigens, such as BiP, RA33 and GPI and also joint specific antigens such as type II collagen (CII), have been reported (5-8).
Since there is no way to cure inflammatory joint diseases today there is a need for developing a way to cure the disease.